There are various conventional methods of chromatographic separation of a starting fluid material containing at least 2 components into the respective components, several representative examples of which include the following methods:
A method (1) is a batchwise one wherein analytical high-performance liquid chromatography is scaled up, and which is generally called preparatory chromatography.
A method (2) is one wherein 2 fractions are obtained from a starting fluid material using a standard simulated moving bed seperator as disclosed in Japanese Patent Publication No. 15,681/1967.
A method (3) is one wherein use is made of an improved simulated moving bed separator, and examples of which include a process comprising a circulation step of simply moving fluid in the downstream direction thereof through a packing bed without fluid feed and fluid withdrawal as disclosed in Japanese Patent Laid-Open No. 49,159/1990 (Japanese Patent Publication No. 46,097/1995) and a process comprising 3 steps including 2 respective steps of separately withdrawing extract and raffinate as disclosed in Japanese Patent Laid-Open No. 100,459/1991. These processes are those wherein 2 fractions are obtained from a starting fluid material.
On the other hand, several representative examples of conventional chromatographic separation methods of separating a starting fluid material containing at least 3 components into at least 3 fractions enriched with respective components include the following methods:
A method (4) is one using either 2 simulated moving bed chromatographic separators for separation of only 2 components or using such a separator twice as disclosed in Japanese Patent Laid-Open No. 124,895/1990. More specifically, a starting solution material is either first separated into a component A and a mixture of components B+C, followed by separation of the mixture of components B+C into the components B and C, or first separated into a mixture of components A+B and the component C, followed by separation of the mixture of components A+B into the components A and B. This is so because separation of only 2 components is possible with an ordinary simulated moving bed chromatographic separator. Thus, in order to actually separate 3 components from one another, either 2 simulated moving bed chromatographic separators must be prepared or one such separator must be used twice. In the latter case, a solution midway of separation (fraction of mixture) must be stored once, followed by using the same separator again under varied conditions.
A method (5) is one disclosed in Japanese Patent Laid-Open No. 227,804/1992, wherein a starting fluid material containing at least 3 components is efficiently and continuously separated into fractions enriched with the respective components with one altered simulated moving bed chromatographic separator packed with one kind of packing (chromatographic packing) by repeating the step of withdrawing a fraction enriched with a component having a medium affinity for packing while feeding desorbent and the starting fluid material and the step of withdrawing fractions respectively enriched with components having respective weak and strong affinities for packing while feeding desorbent.
A method (6) is one disclosed in Japanese Patent Laid-Open No. 232,003/1995, wherein at least 3 fractions are separated from one another with a simulated moving bed separator comprising 4 packing bed units and packed with one kind of packing by repeating the step of withdrawing fractions respectively enriched with components having respective weak and medium affinities for packing while feeding eluent and a starting solution material, the step of circulating liquid in the simulated moving bed without liquid feed and withdrawal, and the step of withdrawing a fraction enriched with a component having a strong affinity for packing while feeding eluent.
A method (7) is one disclosed in Japanese Patent Laid-Open No. 80,409/1989, wherein use is made of an arrangement of separation columns (packed column units having packing bed units) packed with a first packing having the following partition coefficients for components: component A&lt;component B&lt;component C, alternate with separation columns packed with a second packing having the following partition coefficients for components: component A&lt;component C&lt;component B.
The foregoing methods (2) to (7) are fundamentally those whereto application is made either of a standard simulated moving bed procedure comprising an operation of feeding a starting fluid material containing a plurality of components to be separated and desorbent (also called "eluent" in the case of liquid) at respective designated positions to an endless circulation system made up of a plurality of packing bed units packed with chromatographic packing (sorbent such as adsorbent) and linked endlessly for circulation in one direction through the endless circulation system, and withdrawing fractions from zones enriched with respective components out of the endless circulation system while taking advantage of a phenomenon that a plurality of components to be separated are separated into respective zones enriched with the respective components due to a difference between the components in affinity for chromatographic packing, and an operation of intermittently displacing the starting fluid material and desorbent feed positions as well as the fraction withdrawal positions in the direction of fluid flow as if the packing were apparently moved in the direction opposite to that of fluid flow, whereby two fractions enriched with the respective components are continuously obtained from the starting fluid material; or of a procedure of obtaining 2 fractions or at least 3 fractions, which is improved over or altered from the standard simulated moving bed procedure (in the present invention, the "simulated moving bed procedure" is regarded as also encompassing those improved over or altered from the standard simulated moving bed procedure).
Meanwhile, although all the foregoing methods are of the same technology in respect of chromatographic separation of a starting fluid material containing at least 2 components into at least 2 fractions, they involve the following respective problems, or demerits, when they are adopted in industrial-scale equipment for carrying out the separation technology.
The method (1) is poor in separation because it is batchwise, and involves a problem that it is often unfit for industrial-scale separation involving treatment of a large amount of starting solution material because a large amount of eluent must be used.
In the foregoing methods (2) to (7), the separation performance, i.e., the separability of components [relevant to the load (feed rate) of a starting fluid material], the purities and recoveries of components contained as objects of recovery in recovered fractions, the amount of used desorbent, such as eluent, relevant to concentration energy in the later step of concentrating recovered fractions (relevant to the desired component concentrations of the recovered fractions), etc. are generally influenced by packing packed in packing bed units (bed units packed with packing), while involving a problem that a countermeasure for an improvement in respect of one of those influences tends to produce other adverse effects.
The foregoing methods (4) to (7) in particular for separation of at least 3 fractions involve the following specific problems:
The method (4) requires either installing 2 simulated moving bed chromatographic separators or using the same separator twice. Installing 2 simulated moving bed chromatographic separators involves a problem that the equipment cost is increased. Where the same separator is used twice, the same packing must inevitably be used because replacing the packing every time is troublesome in an aspect of operation. This involves a problem that all 3 components cannot efficiently be separated from one another in some cases because of one kind of packing. For example, there arises a case where a component A is too well separated from a component B, but separation of the component B from a component C is so poor that the component purities of fractions are not heightened.
The methods (5) and (6) also involve a problem that there arises a case where all 3 components cannot efficiently be separated because of one kind of packing. For example, there arises a case where a component A is too well separated from a component B, but separation of the component B from a component C is so poor that the component purities of fractions are not heightened.
The method (7) involves a problem that a difficulty is encountered in combining 2 kinds of suitable packings for a starting solution to be subjected to chromatographic separation.
Although it can be said that choice and use of the optimum packing capable of suitably adjusting the foregoing various influences will suffice in order to solve such problems, choice of the optimum packing is not easy as a matter of fact. For example, when the resolution, by packing, of a plurality of components contained in a starting fluid material is enhanced as much as possible in order to heighten the purities and recoveries of components as objects of recovery, intervals between a plurality of zones enriched with respective components are spread too broad in the endless circulation system, whereby the amount of desorbent to be used is increased (the amount of desorbent to be used for desorption of a strong-affinity component in particular is increased because of a large difference between components in affinity for packing), leading to a problem that the component concentrations of respective recovered fractions are lowered. On the other hand, using packing poor in resolution for the purpose of decreasing the amount of desorbent to be used involves a problem that the purities and recoveries of components are lowered. Thus, the chances are rare that there exists any conventional packing suitable in respect of the resolution of a plurality of components to be separated, and creation of a novel packing of that kind is not easy.
Incidentally, the term "resolution," which is a yardstick indicative of the extent of separation of 2 components, is defined as being equal to a value found by dividing the distance between the centers of two adjacent enriched zones (bands) 1 and 2 by an average band width (see "High-Performance Liquid Chromatography" published by Tokyo Kagaku Dozin Co., Ltd. in 1976).
An object of the present invention, which has been made in view of the foregoing problems of the conventional technologies, is to provide process and equipment for efficiently separating components from a starting fluid material containing at least 2 components in chromatographic separation of the components.